Early Dose Intensity of Gleevec® May Optimize Response for Chronic Phase CML

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Early Dose Intensity of Gleevec® May Optimize Response for Chronic Phase CML

Patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML) who receive high doses (600 mg) of Gleevec® (imatinib) in the first year of treatment experience improved molecular response rates, according to the results of a study published in the journal Blood.[1]

Chronic myeloid leukemia (CML), also called chronic granulocytic leukemia, is a cancer that originates in the immune cells. In CML large numbers of young immune cells do not mature, resulting in an excess accumulation of these cells. These leukemia cells then crowd the bone marrow and blood, suppressing formation and function of other blood cells normally present in these areas. In addition, the leukemia cells cannot perform their function properly, leaving patients susceptible to infection.

Chronic myeloid leukemia begins with a chronic phase, during which few clinical problems, if any, occur. However, when left untreated, the chronic phase progresses into acute phases; these phases, called the accelerated and blastic phases, are characterized by fast-growing and aggressive cancer. Patients reaching these acute phases have a poor prognosis for long-term survival.

Standard treatment for CP-CML includes treatment with Gleevec. Several clinical trials have used doses of 400 mg/day; however, newer data has indicated that dose increases up to 800 mg/day have resulted in improved response rates.

In order to examine the impact of dose intensity on molecular responses, researchers with the Australasian Leukaemia and Lymphoma Group (ALLG) conducted a Phase II trial of higher-dose Gleevec in patients with newly diagnosed CP-CML. The study included 103 patients who were enrolled between October 2002 and August 2003. Patients received 600 mg of Gleevec daily, with dose escalation to 800 mg for suboptimal response. The primary endpoints of the study were major molecular response (MMR), major cytogenetic response (MCR), and complete cytogenetic response (CCR).

The estimated cumulative incidence of CCR was 88% at 12 months and 90% at 24 months, and the MMR was 47% at 12 months and 73% at 24 months. Prior to the 12-month mark, 17 patients required the dose escalation to 800 mg (for failure to achieve or maintain MCR at six months or CCR at nine months); however, this dose escalation was possible in only eight of these patients. After 12 months dose escalation was indicated for 73 patients and was possible in 45 of these.

In patients who were able to maintain the daily average of 600 mg/day of Gleevec during the first six months, the MMR rate was 55% at 12 months and 77% at 24 months, compared with 32% at 12 months and 53% at 24 months in patients who averaged less than 600 mg/day.

As a result of the superior responses achieved in patients in this study, the researchers concluded that maintaining Gleevec “dose at 600 mg/day in the first year of therapy for patients with newly diagnosed CML predicts for higher molecular response rates compared with lower doses.”